Trial Outcomes & Findings for Study of Ataluren (PTC124™) in Cystic Fibrosis (NCT NCT00803205)

NCT ID: NCT00803205

Last Updated: 2020-05-14

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

238 participants

Primary outcome timeframe

Baseline (Week 1)

Results posted on

2020-05-14

Participant Flow

A total of 299 male and female participants with nonsense-mutation-mediated cystic fibrosis (nmCF) aged ≥6 years signed the informed consent form and were screened for eligibility, of which 61 did not meet entry criteria to participate in the study.

A total of 238 participants were randomized in a 1:1 ratio to either ataluren or placebo. Six participants (4 in the ataluren arm; 2 in the placebo arm) were excluded from the Intent-to-Treat (ITT) population because they did not have at least 1 post-Baseline forced expiratory volume (FEV1) assessment by Week 8.

Participant milestones

Participant milestones
Measure	Ataluren Participants received ataluren 3 times daily (TID): 10 milligrams/kilogram (mg/kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Overall Study STARTED	120	118
Overall Study Completed Week 16	107	113
Overall Study Completed Week 24	103	110
Overall Study As-Treated Population*	120	118
Overall Study ITT Population	116	116
Overall Study Per Protocol Population	100	103
Overall Study COMPLETED	100	104
Overall Study NOT COMPLETED	20	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Ataluren Participants received ataluren 3 times daily (TID): 10 milligrams/kilogram (mg/kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Overall Study Adverse Event	7	2
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	9	9
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	1	1
Overall Study Medical Monitor Decision	1	0
Overall Study Acquired a Lung Infection	0	1
Overall Study Sponsor Decision	0	1

Baseline Characteristics

Study of Ataluren (PTC124™) in Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ataluren n=120 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=118 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Total n=238 Participants Total of all reporting groups
Age, Continuous	23.0 years STANDARD_DEVIATION 10.06 • n=5 Participants	23.2 years STANDARD_DEVIATION 9.24 • n=7 Participants	23.1 years STANDARD_DEVIATION 9.64 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	59 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	59 Participants n=7 Participants	121 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week 1)

Population: The ITT Population: all randomized participants with data for FEV1 at Baseline and a minimum of 1 post-Baseline assessment before Week 8. Here, 'Number analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in One Second (FEV1) at Baseline	62.092 percentage of predicted FEV1 Standard Deviation 13.6159	60.232 percentage of predicted FEV1 Standard Deviation 15.1437

PRIMARY outcome

Timeframe: End of Treatment (EOT) (Week 48)

Spirometry was used to assess pulmonary function by measuring the percentage of predicted function, which was determined on the basis of the height value obtained at the same study visit, for FEV1 (the amount of air that can be exhaled in 1 second). Spirometry was assessed by using current guidelines of the American Thoracic Society (ATS) and European Respiratory Society (ERS). The percentage of change in percent-predicted of FEV1 was calculated as follows: (\[percent-predicted FEV1-Baseline percent-predicted FEV1\]/Baseline percent-predicted FEV1)\*100. Baseline was the average of percent-predicted FEV1 at screening and randomization. A negative change from Baseline indicates that percent-predicted of FEV1 decreased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Percentage Change From Baseline in Percent-Predicted of FEV1 at Week 48	-2.534 percent change Standard Deviation 13.2452	-5.500 percent change Standard Deviation 12.5595

SECONDARY outcome

Timeframe: Baseline to EOT (Week 48)

A Respiratory Event Form, which collected data on various signs, symptoms, and effects for each event, was completed by the Investigator when informed by the participant of a respiratory event. Pulmonary exacerbations were assessed by using the modified Fuchs' criteria, which defines an exacerbation as a respiratory event requiring treatment with parenteral antibiotics for any 4 of the following 12 symptoms, with or without intravenous antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10% or more from a previously recorded value; or radiographic changes indicative of pulmonary function. The 48-week exacerbation rate was determined by adding the weekly rates for each arm and dividing the sum by 48.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks	1.42 exacerbations Interval 1.05 to 1.79	1.78 exacerbations Interval 1.38 to 2.17

SECONDARY outcome

Timeframe: Baseline, EOT (Week 48)

The frequency of awake cough was measured using the LifeShirt, which incorporates motion-sensing transducers, electrodes, a microphone, and a 3-axis accelerometer into a lightweight vest. The rate was determined by dividing the total number of coughs by 24 (the number of hours of the observation period). Baseline was the latest, valid assessment prior to the treatment. A negative change from Baseline indicates that coughing decreased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in Awake Cough Hourly Rate at Week 48 Baseline	28.218 coughs/hour Standard Deviation 20.2726	24.472 coughs/hour Standard Deviation 16.7828
Change From Baseline in Awake Cough Hourly Rate at Week 48 Change From Baseline	-0.595 coughs/hour Standard Deviation 18.3221	0.882 coughs/hour Standard Deviation 14.3936

SECONDARY outcome

Timeframe: Baseline, EOT (Week 48)

The CFQ-R consists of 44 items, including generic scales of physical functioning, role functioning, vitality, health perceptions, emotional functioning, and social functioning, and CF-specific scales of respiratory and digestive symptoms, body image, eating disturbances, and treatment burden. Each domain score ranges from 1 to 4. Scores were linearly transformed to a 0 to 100 scale, with higher scores indicating better health. Domain scores were calculated by using the following formula: 100 \* (sum of responses - minimum possible sum)/ (maximum possible sum - minimum possible sum). The minimum possible sum = number of questions \* 1; the maximum possible = the number of questions \* 4. Baseline was the latest, valid assessment prior to the treatment. A negative change from Baseline indicates that health has worsened. Participants may have switched age groups during the study.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in the Respiratory Domain Score of the Revised Cystic Fibrosis Questionnaire (CFQ-R) at Week 48 Aged 6-13 years, Change From Baseline	-0.69 units on a scale Standard Deviation 12.028	-3.57 units on a scale Standard Deviation 21.973
Change From Baseline in the Respiratory Domain Score of the Revised Cystic Fibrosis Questionnaire (CFQ-R) at Week 48 Aged 6-13 years, Baseline	77.78 units on a scale Standard Deviation 11.070	79.49 units on a scale Standard Deviation 16.879
Change From Baseline in the Respiratory Domain Score of the Revised Cystic Fibrosis Questionnaire (CFQ-R) at Week 48 Age ≥14 years , Baseline	70.06 units on a scale Standard Deviation 15.678	65.95 units on a scale Standard Deviation 16.771
Change From Baseline in the Respiratory Domain Score of the Revised Cystic Fibrosis Questionnaire (CFQ-R) at Week 48 Age ≥14 years, Change From Baseline	-2.81 units on a scale Standard Deviation 18.365	-3.32 units on a scale Standard Deviation 16.245

SECONDARY outcome

Timeframe: Baseline (Week 1)

Population: The ITT Population: all randomized participants with data for FEV1 at Baseline and a minimum of 1 post-Baseline assessment before Week 8. Here, 'Number analyzed 'signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Percent-Predicted of Forced Vital Capacity (FVC) at Baseline	78.332 percentage of predicted FVC Standard Deviation 13.1825	76.609 percentage of predicted FVC Standard Deviation 13.3711

SECONDARY outcome

Timeframe: EOT (Week 48)

Population: The ITT Population: all randomized participants with data for FEV1 at Baseline and a minimum of 1 post-Baseline assessment before Week 8. Here, 'Number analyzed 'signifies participants evaluable for this outcome measure.

Spirometry was used to assess pulmonary function by measuring the percentage of predicted function, which was determined on the basis of the height value obtained at the same study visit, for FVC (the amount of air that can be exhaled after taking a deep breath). Spirometry was assessed by using current guidelines of the ATS and ERS. The percentage of change in percent-predicted of FVC was calculated as follows: ((percent-predicted FVC-Baseline percent-predicted FVC)/Baseline percent-predicted FVC)\*100. Baseline was the average of percent-predicted FVC at screening and randomization. A negative change from Baseline indicates that percent-predicted of FVC decreased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Percentage Change From Baseline in Percent-Predicted of FVC at Week 48	-2.139 percent change Standard Deviation 10.0463	-3.484 percent change Standard Deviation 9.9304

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD)

Population: The As-Treated Population: all randomized participants who received at least 1 dose of study drug.

A TEAE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship that occurred or worsened in the period extending from first dose of study drug to 4 weeks after the last dose of study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. AE severity was graded as follows: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: fatal. A TEAE was considered related if in the opinion of the Investigator it was possibly or probably caused by the study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Adverse Events module.

Outcome measures

Outcome measures
Measure	Ataluren n=120 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=118 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Grade 3 TEAE	15.8 percent of participants	25.4 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Grade 4 TEAE	0 percent of participants	0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Grade 5 TEAE	0 percent of participants	0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Unrelated TEAE	25.0 percent of participants	35.6 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Unlikely related TEAE	32.5 percent of participants	26.3 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Possibly related TEAE	28.3 percent of participants	29.7 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Probably related TEAE	12.5 percent of participants	5.9 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Discontinuation due to TEAE	6.7 percent of participants	2.5 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Serious TEAE	37.5 percent of participants	40.7 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) At least 1 TEAE	98.3 percent of participants	97.5 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Grade 1 TEAE	15.0 percent of participants	16.9 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) Grade 2 TEAE	67.5 percent of participants	55.1 percent of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to EOT (Week 48)

Population: The As-Treated Population: all randomized participants who received at least 1 dose of study drug.

Study drug compliance was assessed by using a Pharmacy Subject Study Drug Accountability Log (completed by the investigational site personnel). The rate of compliance was defined as 100 \* (number of sachets taken/number of planned sachets) during the study. All calculations were based on the records of the first dose date to the last dose date. To differentiate dose strengths while maintaining the blind, each kit had a unique kit number and had prominent lettering "A" and "B." Each kit contained 65 packets of 1 of the dose strengths (125, 250, or 1000 mg or matching placebo). Labeling for active drug and placebo was identical.

Outcome measures

Outcome measures
Measure	Ataluren n=120 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=118 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Rate of Study Drug Compliance by Drug Accountability Drug Kit A	90.149 percent of doses taken Interval 18.24 to 109.24	85.119 percent of doses taken Interval 28.36 to 125.79
Rate of Study Drug Compliance by Drug Accountability Drug Kit B	90.830 percent of doses taken Interval 13.27 to 116.67	86.614 percent of doses taken Interval 25.22 to 107.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to EOT (Week 48)

Population: The As-Treated Population: all randomized participants who received at least 1 dose of study drug.

Patient-reported data were obtained from the participant's electronic daily diary, which was completed by the participant or the caregiver. During study treatment, the electronic daily diary was to be completed by the participant or caregiver each day for each dose. For each participant, compliance is described in terms of the percentage of study drug actually taken. All calculations were based on the records of the first dose date to the last dose date. To differentiate dose strengths while maintaining the blind, each kit had a unique kit number and had prominent lettering "A" and "B." Each kit contained 65 packets of 1 of the dose strengths (125, 250, or 1000 mg or matching placebo). Labeling for active drug and placebo was identical.

Outcome measures

Outcome measures
Measure	Ataluren n=120 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=118 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Rate of Study Drug Compliance by Patient-Reported Data	71.48 percent of doses taken Interval 0.0 to 98.5	69.27 percent of doses taken Interval 6.4 to 98.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Predose and 2 Hours Postdose at Week 1, Week 16, Week 32, EOT (Week 48)

Population: The As-Treated Population: all randomized participants who received at least 1 dose of study drug.

Blood samples were drawn immediately before administration of the first daily dose (dose taken with breakfast) of study drug and 2 hours after the first daily dose. Whenever possible, the pre-dose sample was to be obtained within 15 minutes of drug administration. Participants in the Placebo arm did not receive Ataluren and are not included in this Outcome Measure.

Outcome measures

Outcome measures
Measure	Ataluren n=120 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Concentration of Ataluren Week 1 Predose	0 micrograms/milliliter (ug/mL) Interval 0.0 to 0.0	—
Concentration of Ataluren Week 1 Postdose	14.100 micrograms/milliliter (ug/mL) Interval 1.42 to 56.4	—
Concentration of Ataluren Week 16 Predose	4.350 micrograms/milliliter (ug/mL) Interval 0.0 to 52.6	—
Concentration of Ataluren Week 16 Postdose	11.900 micrograms/milliliter (ug/mL) Interval 0.8 to 41.9	—
Concentration of Ataluren Week 32 Predose	4.630 micrograms/milliliter (ug/mL) Interval 0.0 to 29.2	—
Concentration of Ataluren Week 32 Postdose	13.400 micrograms/milliliter (ug/mL) Interval 2.37 to 36.3	—
Concentration of Ataluren Week 48 Predose	3.970 micrograms/milliliter (ug/mL) Interval 0.0 to 27.0	—
Concentration of Ataluren Week 48 Postdose	10.500 micrograms/milliliter (ug/mL) Interval 0.0 to 39.1	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to EOT (Week 48)

During treatment, any intervention including hospitalization or use of oral, inhaled, or intravenous antibiotics was documented if it was due to an exacerbation-like episode. Participants and caregivers recorded interventions in an electronic diary. The rate of interventions was defined as the total days with interventions divided by the total study duration.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Rate of Interventions for Respiratory Symptoms Hospitalization	0.010 days with interventions per study Standard Deviation 0.0222	0.021 days with interventions per study Standard Deviation 0.0469
Rate of Interventions for Respiratory Symptoms Use of Antibiotics	0.220 days with interventions per study Standard Deviation 0.2284	0.245 days with interventions per study Standard Deviation 0.2380

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to EOT (Week 48)

During treatment, any disruption in the activities of daily living, such as missed school or work, was documented if it was due to an exacerbation-like episode. Participants and caregivers recorded all disruptions in an electronic diary. The rate of disruptions was defined as the total days with disruptions to daily living divided by the total study duration.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Rate of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms	0.037 days with disruptions per study Standard Deviation 0.0550	0.047 days with disruptions per study Standard Deviation 0.0755

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

Participants were weighed, and the weight was recorded at Baseline and then every 8 weeks during the treatment period. Baseline was the latest valid assessment prior to the treatment. A positive change from Baseline indicates that weight increased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in Body Weight at Week 48 Baseline	53.46 kg Standard Deviation 13.941	56.01 kg Standard Deviation 13.149
Change From Baseline in Body Weight at Week 48 Change From Baseline	0.87 kg Standard Deviation 3.342	0.83 kg Standard Deviation 3.101

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

Expression of IL-8 was measured in serum and in sputum. Sputum was spontaneously produced and tested by using standardized procedures developed by the Cystic Fibrosis Foundation Therapeutics, Inc. Therapeutics Development Network (CFFT-TDN). Baseline was the latest valid assessment prior to the treatment. A negative change from Baseline indicates that the concentration of IL-8 decreased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in the Concentration of Interleukin-8 (IL-8) in Serum and Sputum at Week 48 Sputum, Change From Baseline	28882.79 picograms/mL Standard Deviation 199160.845	9957.24 picograms/mL Standard Deviation 166348.660
Change From Baseline in the Concentration of Interleukin-8 (IL-8) in Serum and Sputum at Week 48 Serum, Baseline	39.537 picograms/mL Standard Deviation 14.1697	55.845 picograms/mL Standard Deviation 131.8505
Change From Baseline in the Concentration of Interleukin-8 (IL-8) in Serum and Sputum at Week 48 Serum, Change From Baseline	-2.334 picograms/mL Standard Deviation 13.2141	-16.197 picograms/mL Standard Deviation 138.3108
Change From Baseline in the Concentration of Interleukin-8 (IL-8) in Serum and Sputum at Week 48 Sputum, Baseline	267629.93 picograms/mL Standard Deviation 259089.569	250170.95 picograms/mL Standard Deviation 180581.976

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

Expression of neutrophil elastase was measured in sputum. Sputum was spontaneously produced and tested by using standardized procedures developed by the CFFT-TDN. Baseline was the latest valid assessment prior to the treatment. A positive change from Baseline indicates that the concentration of neutrophil elastase increased.

Outcome measures

Outcome measures
Measure	Ataluren n=94 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=94 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in the Concentration of Neutrophil Elastase in Sputum at Week 48 Baseline	183.64 ug/mL Standard Deviation 221.901	227.35 ug/mL Standard Deviation 227.881
Change From Baseline in the Concentration of Neutrophil Elastase in Sputum at Week 48 Change From Baseline	5.45 ug/mL Standard Deviation 232.824	-8.67 ug/mL Standard Deviation 296.105

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

Expression of CRP was measured in serum. Baseline was the latest valid assessment prior to the treatment. A positive change from Baseline indicates that CRP concentration increased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in the Concentration of C-Reactive Protein (CRP) in Serum at Week 48 Baseline	6.899 mg/liter (L) Standard Deviation 11.5869	7.037 mg/liter (L) Standard Deviation 8.4411
Change From Baseline in the Concentration of C-Reactive Protein (CRP) in Serum at Week 48 Change From Baseline	2.420 mg/liter (L) Standard Deviation 10.5162	2.031 mg/liter (L) Standard Deviation 10.1202

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

Lungs were imaged by using non-contrast, spiral CT. The total lung score for each CT scan was established by the sum of 5 characteristics from the Brody scoring system, with scores ranging from 0 to 40.5, with lower scores indicating better lung function. The characteristics scored were bronchiectasis (score range 0 - 12), mucus plugging (score range 0- 6), peribronchial thickening (score range 0 - 9), parenchyma (score range 0 - 9), and hyperinflation (score range 0 - 4.5). Baseline was the latest valid assessment prior to the treatment. A positive change from Baseline indicates that lung function worsened.

Outcome measures

Outcome measures
Measure	Ataluren n=105 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=106 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in the Total Lung Score as Assessed by Computed Tomography (CT) at Week 48 Baseline	9.531 units on a scale Standard Deviation 3.7526	9.619 units on a scale Standard Deviation 3.4244
Change From Baseline in the Total Lung Score as Assessed by Computed Tomography (CT) at Week 48 Change From Baseline	0.282 units on a scale Standard Deviation 1.3441	0.560 units on a scale Standard Deviation 1.5602

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

TEPD was assessed in each nostril using standardized equipment, techniques, and solutions. Assessments were made on the nasal epithelium cells lining the inferior turbinate. Warmed solutions of Ringer's solution, amiloride, chloride-free gluconate, isoproterenol, and adenosine triphosphate (ATP) were perfused for ≥3-minute sequentially through a nasal catheter while a voltage tracing was recorded. Total chloride transport was computed for each nostril. The total chloride transport values were calculated by subtracting the voltages at the end of a perfusion from the voltage at the end of an earlier perfusion (isoproterenol - amiloride). The average of the values for each nostril was computed. If the assessment was available in only 1 nostril, this value was used as if it were the average of both nostrils. Baseline was the latest, valid assessment prior to the treatment. A positive change from Baseline indicates that nasal chloride transport increased.

Outcome measures

Outcome measures
Measure	Ataluren n=116 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=116 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in Total Nasal Chloride Transport as Assessed by Transepithelial Potential Difference (TEPD) at Week 48 Change From Baseline	0.312 millivolts Standard Deviation 5.0574	0.139 millivolts Standard Deviation 5.8139
Change From Baseline in Total Nasal Chloride Transport as Assessed by Transepithelial Potential Difference (TEPD) at Week 48 Baseline	1.578 millivolts Standard Deviation 3.8786	1.950 millivolts Standard Deviation 3.5462

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, EOT (Week 48)

Sweat was collected, from each arm, by using pilocarpine iontophoresis. The chloride concentration in the sweat was quantified for each arm by using standard laboratory methods. Tests were also considered valid if the sweat collection time was ≤35 minutes; tests with longer collection times were also considered valid if extra time was needed to obtain sufficient volume (≥15uL) for analysis. For analysis purposes, the average of the values from each arm were computed. If the assessment was valid and/or available in only 1 arm, this value was used as if it were the average of both arms. The method used was consistent with the CFFT-TDN guidelines. Baseline was the latest, valid assessment prior to the treatment. A negative change from Baseline indicates that sweat chloride concentration decreased.

Outcome measures

Outcome measures
Measure	Ataluren n=114 Participants Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=111 Participants Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Change From Baseline in Sweat Chloride Concentration at Week 48 Change From Baseline	-1.325 millimoles/L Standard Deviation 8.9431	-0.619 millimoles/L Standard Deviation 10.2657
Change From Baseline in Sweat Chloride Concentration at Week 48 Baseline	100.140 millimoles/L Standard Deviation 14.2170	96.586 millimoles/L Standard Deviation 15.9279

Adverse Events

Ataluren

Serious events: 46 serious events

Other events: 118 other events

Deaths: 0 deaths

Placebo

Serious events: 50 serious events

Other events: 115 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Patient Advocacy

PTC Therapeutics, Inc.

Phone: 1-866-562-4620

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ataluren n=120 participants at risk Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=118 participants at risk Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Gastrointestinal disorders Haematemesis	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intussusception	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
General disorders Drug withdrawal syndrome	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Biliary colic	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Immune system disorders Drug hypersensitivity	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	1.7% 2/120 • Number of events 2 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Appendicitis	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia mycoplasmal	0.83% 1/120 • Number of events 2 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchopulmonary aspergillosis allergic	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Mycobacterium abscessus infection	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	1.7% 2/118 • Number of events 2 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Joint injury	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Anorexia	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Hypercreatinaemia	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Depression	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal failure	2.5% 3/120 • Number of events 3 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal failure acute	2.5% 3/120 • Number of events 3 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal colic	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary retention	0.83% 1/120 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.00% 0/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cystic fibrosis long	28.3% 34/120 • Number of events 47 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	34.7% 41/118 • Number of events 66 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.7% 2/120 • Number of events 2 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	2.5% 3/118 • Number of events 3 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Vascular disorders Thrombosis	0.00% 0/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Number of events 1 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.

Measure	Ataluren n=120 participants at risk Participants received ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.	Placebo n=118 participants at risk Participants received placebo TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total daily dose 40 mg/kg). Treatment continued for 48 weeks, after which participants were followed for 4 weeks.
Gastrointestinal disorders Abdominal pain	16.7% 20/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	11.9% 14/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	11.7% 14/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	9.3% 11/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	10.8% 13/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	17.8% 21/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	9.2% 11/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	5.9% 7/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	9.2% 11/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	11.0% 13/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	5.8% 7/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	7.6% 9/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	14.2% 17/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	18.6% 22/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	9.2% 11/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	9.3% 11/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Viral upper respiratory tract infection	17.5% 21/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	27.1% 32/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Sinusitis	12.5% 15/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	11.9% 14/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Rhinitis	10.0% 12/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	11.0% 13/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	8.3% 10/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	6.8% 8/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pharyngitis	5.8% 7/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	3.4% 4/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	4.2% 5/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	10.2% 12/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Abnormal loss of weight	8.3% 10/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	4.2% 5/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	6.7% 8/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	5.1% 6/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Hypercreatinaemia	6.7% 8/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	16.7% 20/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	11.9% 14/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Nephrolithiasis	6.7% 8/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	3.4% 4/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Dysuria	5.8% 7/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	0.85% 1/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cystic fibrosis lung	70.8% 85/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	69.5% 82/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	23.3% 28/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	29.7% 35/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	10.0% 12/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	9.3% 11/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.5% 9/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	13.6% 16/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Rales	5.0% 6/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	5.1% 6/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	4.2% 5/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	6.8% 8/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 4/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	11.9% 14/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.83% 1/120 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.	5.1% 6/118 • Baseline up to 4 Weeks Post-Treatment (Week 52) or Premature Discontinuation (PD) The As-Treated Population: all randomized participants who received at least 1 dose of study drug.